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Rosnah Sutan,1 May Luu Yeong,1 Zaleha Abdullah Mahdy,2 Ahmad Shuhaila,2 Jaafar Rohana,3 Shareena Ishak,3 Khadijah Shamsuddin,1 Aniza Ismail,1 Idayu Badillah Idris,1 Saperi Sulong4 1Department of Community Health, 2Department of Obstetrics and Gynecology, 3Department of Pediatrics, 4Department of Medical Records, Universiti Kebangsaan Malaysia Medical Center, Kuala Lumpur, Malaysia Introduction: The aim of this study was to determine the trend of head circumference as predictor of microcephaly among term infants born in a teaching hospital in Malaysia from 2011 to 2015. Methodology: This was a cross-sectional study using data from the electronic birth census. The independent variables were mothers’ age and height, parity, birth weight and birth length. All term newborns, both alive and stillbirth, with 37–41 completed gestational weeks, and a birth weight of at least 500 g was extracted from the census. Results: A total of 26,503 newborns fulfilled the inclusion criteria (13,655 males, 12,840 females). The mean head circumferences for male and female newborns were 32.93 cm (± SD 1.32) and 32.56 cm (± SD 1.31). The average head circumference for Malaysian newborns was found to be smaller than the World Health Organization Standard Growth Chart for Term Infant. A total of 17.6% (n=4,669) of the total samples were observed to have microcephaly. Among them, 73.2% (n=3,419) were non-proportionate microcephaly with normal birth weight of 2.5kg and above. Bivariate analyses showed that all independent variables were significant predictors of microcephaly. Both simple and multiple logistic regressions demonstrated that low birth weight was the most significant predictors for microcephaly (adjusted OR 12.14, 95% CI 10.80, 13.65). Conclusion: There is an increasing trend of microcephaly across the years and the low birth weight was noted as the main predictor of microcephaly. Future studies are needed to determine the possible cause of increasing microcephaly by controlling for birth weight and gestational age of the neonates. Keywords: SGA, perinatal, growth chart, IUGR, birth parameter, occipito-frontal

Azuana Ramli,1,3 Syed Mohamed Aljunid,1,2 Saperi Sulong,2 Faridah Aryani Md Yusof31United Nations University International Institute for Global Health (UNU-IIGH), Kuala Lumpur, Malaysia; 2International Centre for Casemix and Clinical Coding (ITCC), Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia; 3Pharmaceutical Services Division, Ministry of Health, Petaling Jaya, MalaysiaPurpose: HMG-CoA reductase inhibitors (statins) are extensively used in treating hypercholesterolemia. The statins available in Malaysia include atorvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, and fluvastatin. Over the years, they have accumulated in the National Drug Formulary; hence, the need for review. Effective selection of the best drugs to remain in the formulary can become complex due to the multiple drug attributes involved, and is made worse by the limited time and resources available. The multiattribute scoring tool (MAST) systematizes the evaluation of the drug attributes to facilitate the drug selection process. In this study, a MAST framework was developed to rank the statins based on their utilities or benefits.Methods: Published literature on multicriteria decision analysis (MCDA) were studied and five sessions of expert group discussions were conducted to build the MAST framework and to review the evidence. The attributes identified and selected for analysis were efficacy (clinical efficacy, clinical endpoints), safety (drug interactions, serious side effects and documentation), drug applicability (drug strength/formulation, indications, dose frequency, side effects, food–drug interactions, and dose adjustments), and cost. The average weights assigned by the members for efficacy, safety, drug applicability and cost were 32.6%, 26.2%, 24.1%, and 17.1%, respectively. The utility values of the attributes were scored based on the published evidence or/and agreements during the group discussions. The attribute scores were added up to provide the total utility score.Results: Using the MAST, the six statins under review were successfully scored and ranked. Atorvastatin scored the highest total utility score (TUS) of 84.48, followed by simvastatin (83.11). Atorvastatin and simvastatin scored consistently high, even before drug costs were included. The low scores on the side effects for atorvastatin were compensated for by the higher scores on the clinical endpoints resulting in a higher TUS for atorvastatin. Fluvastatin recorded the lowest TUS.Conclusion: The multiattribute scoring tool was successfully applied to organize decision variables in reviewing statins for the formulary. Based on the TUS, atorvastatin is recommended to remain in the formulary and be considered as first-line in the treatment of hypercholesterolemia.Keywords: multicriteria decision analysis, utility score, drug attributes, drug selection

The emergence of additional chromosome abnormalities (ACAs) in chronic myeloid leukemia (CML) patients during treatment with a tyrosine kinase inhibitor (TKI) regime is generally associated with resistance to treatment and a sign of disease progression to accelerated phase or blast phase. We report the type, frequency, and differential prognostic impact of stratified ACAs with treatment response in 251 Malaysian CML patients undergoing TKI therapy. ACAs were observed in 40 patients (15.9%) of which 7 patients (17.5%) showed ACAs at time of initial diagnosis whereas 33 patients (82.5%) showed ACAs during the course of IM treatment. In order to assess the prognostic significance, we stratified the CML patients with ACAs into four groups, group 1 (+8/+Ph), group 2 (hypodiploidy), group 3 (structural/complex abnormalities); group 4 (high-risk complex abnormalities), and followed up the disease outcome of patients. Group 1 and group 2 relatively showed good prognosis while patients in group 3 and group 4 had progressed or transformed to AP or blast phase with a median survival rate of 12 months after progression. Novel ACAs consisting of rearrangements involving chromosome 11 and chromosome 12 were found to lead to myeloid BP while ACAs involving the deletion of 7q or monosomy 7 led toward a lymphoid blast phase. There was no evidence of group 2 abnormalities (hypodiploidy) contributing to disease progression. Compared to group 1 abnormalities, CML patients with group 3 and group 4 abnormalities showed a higher risk for disease progression. We conclude that the stratification based on individual ACAs has a differential prognostic impact and might be a potential novel risk predictive system to prognosticate and guide the treatment of CML patients at diagnosis and during treatment.

This paper assesses the performances of a downlink cooperative non-orthogonal multiple access (C-NOMA) network over Nakagami-m fading channels. The analytical outage probability expression for each user is derived and verified by Monte Carlo simulations. Based upon the outage probability, the maximal throughputs are obtained and analyzed under different channel conditions. Furthermore, the effects of channel fading on the probability and throughput are investigated. The results indicate that the performance of the C-NOMA system is excellent over the source-relay link with less fading. This analysis can be used for designing the C-NOMA systems in the future fifth-generation wireless communication.

This study investigates the superiority of cooperative broadcast transmission over traditional orthogonal schemes when applied in a downlink relaying broadcast channel (RBC). Two proposed cooperative broadcast transmission protocols, one with an amplify-and-forward (AF) relay, and the other with a repetition-based decode-and-forward (DF) relay, are investigated. By utilizing superposition coding (SupC), the source and the relay transmit the private user messages simultaneously instead of sequentially as in traditional orthogonal schemes, which means the channel resources are reused and an increased channel degree of freedom is available to each user, hence the half-duplex penalty of relaying is alleviated. To facilitate a performance evaluation, theoretical outage probability expressions of the two broadcast transmission schemes are developed, based on which, we investigate the minimum total power consumption of each scheme for a given traffic requirement by numerical simulation. The results provide details on the overall system performance and fruitful insights on the essential characteristics of cooperative broadcast transmission in RBCs. It is observed that better overall outage performances and considerable power gains can be obtained by utilizing cooperative broadcast transmissions compared to traditional orthogonal schemes.

Consumer demand for high speed data communication system is increasing day by day. However the major challenges for wireless communication system are Inter Symbol Interference (ISI) and Inter Carrier Interference (ICI) that occur during data transmission. This interference will distort signal and increase error rate in the system. Combination of Orthogonal Frequency Division Multiplexing (OFDM) and Multiple Input Multiple Output (MIMO) give a reliable high data rate. Discrete Cosine Transform (DCT)-based channel estimation is used in STBC MIMO-OFDM and simulated using MATLAB software. The system performance is compared with multiple antenna configuration and different modulation technique. Multiple antenna configurations that involve during simulation are 2x2, 4x4 and 6x6 while modulation techniques are Quadrature Amplitude Modulation (QAM) and Quadrature Phase Shift Keying (QPSK). This simulation will prove that the higher number of transmit and receive antenna, the lower BER for the system.

This paper study the channel estimation based on the exponentially weighted (EW) RLS algorithm. The advantages of the proposed estimator arise from its implementation in the time-domain, whereas fewer channel parameters are required to be estimated compared with the frequency-domain channel coefficients. In addition, the matrix inversion operation required in LS and LMMSE estimators is avoided here by recursively updating the channel estimates. Therefore, the computational complexity is highly reduced compared to frequency-domain based channel estimation. Furthermore, the proposed estimator has good tracking capability due to exploiting the time correlation between the path gains. This paper provides analysis, evaluation and computer simulations in MATLAB. The performance is evaluated in terms of the MSE of the channel estimate and BER for different Doppler frequencies (correspond to different mobility speeds) and Monte Carlo simulations are performed and the MSE and BER performance versus SNR are obtained by averaging over 10000 channel realization. For comparisons, the BER performance is also presented for perfectly known channel at the receiver. In all the simulations, perfect synchronization between the transmitter and the receiver is assumed.

Abstract Background Pneumococcal disease is the leading cause of vaccine-preventable death in children younger than 5 years of age worldwide. The World Health Organization recommends pneumococcal conjugate vaccine as a priority for inclusion into national childhood immunization programmes. Pneumococcal vaccine has yet to be included as part of the national vaccination programme in Malaysia although it has been available in the country since 2005. This study sought to estimate the disease burden of pneumococcal disease in Malaysia and to assess the cost effectiveness of routine infant vaccination with PCV7. Methods A decision model was adapted taking into consideration prevalence, disease burden, treatment costs and outcomes for pneumococcal disease severe enough to result in a hospital admission. Disease burden were estimated from the medical records of 6 hospitals. Where local data was unavailable, model inputs were obtained from international and regional studies and from focus group discussions. The model incorporated the effects of herd protection on the unvaccinated adult population. Results At current vaccine prices, PCV7 vaccination of 90% of a hypothetical 550,000 birth cohort would incur costs of RM 439.6 million (US$128 million). Over a 10 year time horizon, vaccination would reduce episodes of pneumococcal hospitalisation by 9,585 cases to 73,845 hospitalisations with cost savings of RM 37.5 million (US$10.9 million) to the health system with 11,422.5 life years saved at a cost effectiveness ratio of RM 35,196 (US$10,261) per life year gained. Conclusions PCV7 vaccination of infants is expected to be cost-effective for Malaysia with an incremental cost per life year gained of RM 35,196 (US$10,261). This is well below the WHO's threshold for cost effectiveness of public health interventions in Malaysia of RM 71,761 (US$20,922).

Background: The management of docking site healing in bone transport remains a significant challenge in orthopedic surgery. Traditional assessment methods rely heavily on qualitative radiographic evaluations. This study investigates the utility of pixel value ratio (PVR), an objective quantitative measure, in assessing bone healing at the docking site during bone transport., Methods: This retrospective study included 47 patients who underwent bone transport for lower limb reconstruction between January 2015 and January 2020. Patients were categorized into bone union (n = 35) and nonunion (n = 12) groups based on docking site outcomes. PVR was calculated using two methods (PVR1 and PVR2) at six time points over 24 months post-docking. Subgroup analyses were performed based on gender, age, and surgical site., Results: Of 47 patients, 35 achieved bone union and 12 experienced nonunion. Both PVR1 and PVR2 were consistently lower in the union group compared to the nonunion group at all time points (p < 0.001). In the union group, PVR1 ranged from 1.064 ± 0.050 to 1.108 ± 0.062, while PVR2 ranged from 0.926 ± 0.079 to 0.946 ± 0.062. In the nonunion group, PVR1 ranged from 1.204 ± 0.057 to 1.273 ± 0.020, and PVR2 from 1.039 ± 0.060 to 1.148 ± 0.022. Subgroup analyses revealed that males had significantly lower PVR values compared to females, and tibial cases had lower PVR values compared to femoral cases in both union and nonunion groups (p < 0.05). All juvenile patients achieved union, compared to 71.4% of adults (p < 0.01)., Conclusion: PVR demonstrates significant potential as an objective tool for assessing docking site healing in bone transport procedures. The distinct patterns observed between union and nonunion cases provide a foundation for developing clinical guidelines to monitor and predict healing outcomes. Integration of PVR assessment into clinical practice could improve decision-making and optimize treatment protocols in bone transport procedures., (© 2024. The Author(s).)

Background: Muscle atrophy caused by denervation is common in neuromuscular diseases, leading to loss of muscle mass and function. However, a comprehensive understanding of the overall molecular network changes during muscle denervation atrophy is still deficient, hindering the development of effective treatments., Method: In this study, a sciatic nerve transection model was employed in male C57BL/6 J mice to induce muscle denervation atrophy. Gastrocnemius muscles were harvested at 3 days, 2 weeks, and 4 weeks post-denervation for transcriptomic and proteomic analysis. An integrative multi-omics approach was utilized to identify key genes essential for disease progression. Targeted proteomics using PRM was then employed to validate the differential expression of central genes. Combine single-nucleus sequencing results to observe the expression levels of PRM-validated genes in different cell types within muscle tissue.Through upstream regulatory analysis, NRF2 was identified as a potential therapeutic target. The therapeutic potential of the NRF2-targeting drug Omaveloxolone was evaluated in the mouse model., Result: This research examined the temporal alterations in transcripts and proteins during muscle atrophy subsequent to denervation. A comprehensive analysis identified 54,534 transcripts and 3,218 proteins, of which 23,282 transcripts and 1,852 proteins exhibited statistically significant changes at 3 days, 2 weeks, and 4 weeks post-denervation. Utilizing multi-omics approaches, 30 hubgenes were selected, and PRM validation confirmed significant expression variances in 23 genes. The findings highlighted the involvement of mitochondrial dysfunction, oxidative stress, and metabolic disturbances in the pathogenesis of muscle atrophy, with a pronounced impact on type II muscle fibers, particularly type IIb fibers. The potential therapeutic benefits of Omaveloxolone in mitigating oxidative stress and preserving mitochondrial morphology were confirmed, thereby presenting novel strategies for addressing muscle atrophy induced by denervation. GSEA analysis results show that Autophagy, glutathione metabolism, and PPAR signaling pathways are significantly upregulated, while inflammation-related and neurodegenerative disease-related pathways are significantly inhibited in the Omaveloxolone group.GSR expression and the GSH/GSSG ratio were significantly higher in the Omaveloxolone group compared to the control group, while MuSK expression was significantly lower than in the control group., Conclusion: In our study, we revealed the crucial role of oxidative stress, glucose metabolism, and mitochondrial dysfunction in denervation-induced muscle atrophy, identifying NRF2 as a potential therapeutic target. Omaveloxolone was shown to stabilize mitochondrial function, enhance antioxidant capacity, and protect neuromuscular junctions, thereby offering promising therapeutic potential for treating denervation-induced muscle atrophy., (© 2024. The Author(s).)

Background : The link between rheumatoid arthritis (RA) and schizophrenia (SZ) has long been a hot topic of deliberation among scientists from various fields. Especially when it comes to genetics, the connection between RA and SZ is still up for discussion, as can be observed in this study. The HLA genes are the most disputed in identifying a connection between the two diseases, but a more thorough investigation of other genes that may be ignored could yield something even more interesting. Thus, finding the genes responsible for this long-sought relationship will necessitate looking for them. Materials and Methods : Shared and overlapped associated genes involved between SZ and RA were extracted from four databases. The overlapping genes were examined using Database for Annotation, Visualization and Integrated Discovery (DAVID) and InnateDB to search the pertinent genes that concatenate between these two disorders. Results : A total of 91 overlapped genes were discovered, and that 13 genes, divided into two clusters, showed a similarity in function, suggesting that they may serve as an important meeting point. FCGR2A , IL18R , BTNL2 , AGER , and CTLA4 are five non-HLA genes related to the immune system, which could lead to new discoveries about the connection between these two disorders. Conclusion : An in-depth investigation of these functionally comparable non-HLA genes that overlap could reveal new interesting information in both diseases. Understanding the molecular and immune-related aspects of RA and SZ may shed light on their etiology and inform future research on targeted treatment strategies., (Copyright ©2024, Yale Journal of Biology and Medicine.)

Background/objectives: Idiopathic clubfoot is a complex pediatric foot deformity. The Ponseti technique is widely regarded as the standard for correcting deformities, and treatment compliance is essential for preventing relapse. Examining psychosocial effects on parents and/or children during clubfoot treatment provides valuable insights for improving compliance. This scoping review will map the existing literature on the psychological and social effects experienced by parents and/or children with idiopathic clubfoot. It also aims to examine the assessment tools used to measure these impacts and identify factors influencing treatment compliance., Methods: This review will adhere to the Joanna Briggs Institute (JBI) guidelines for scoping reviews. The search will include databases such as Scopus, Web of Science, EBSCOhost, MEDLINE, and PsycINFO and focus on studies published in the last 10 years. This review will include quantitative, qualitative, and mixed-method studies that investigate the psychological and social effects experienced by parents or affected children of any age with idiopathic clubfoot. Reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) extension guidelines. The screening and data extraction process will involve two independent reviewers. The analysis will be descriptive and qualitative., Results: The findings will be presented in tables and a narrative summary., Conclusion: This review may guide health practitioners in developing evidence-based interventions to improve treatment adherence.

Objective: To compare the effects of hypoxia-inducible drugs using deferoxamine (DFO) and accordion technique (AT) on activating the hypoxia-inducible factor 1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway to promote bone regeneration and remodelling during consolidation phase of distraction osteogenesis (DO)., Methods: Forty-five specific-pathogen-free adult male Sprague-Dawley (SD) rats were randomly divided into the control group, DFO group, and AT group, with 15 rats in each group. All rats underwent osteotomy to establish a right femur DO model. Then, continuous distraction was started for 10 days after 5 days of latency in each group. During the consolidation phase after distraction, no intervention was performed in the control group; DFO was locally perfused into the distraction area in the DFO group starting at the 3rd week of consolidation phase; cyclic stress stimulation was given in the AT group starting at the 3rd week of consolidation phase. The general condition of rats in each group was observed. X-ray films were conducted at the end of the distraction phase and at the 2nd, 4th, and 6th weeks of the consolidation phase to observe the calcification in the distraction area. At the 4th and 6th weeks of the consolidation phase, peripheral blood was taken for ELISA detection (HIF-1α, VEGF, CD31, and Osterix), femoral specimens were harvested for gross observation, histological staining (HE staining), and immunohistochemical staining [HIF-1α, VEGF, osteopontin (OPN), osteocalcin (OCN)]. At the 6th week of the consolidation phase, Micro-CT was used to observe the new bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular separation (Tb.Sp), trabecular number (Tb.N), and trabecular thickness (Tb.Th) in the distraction area, and biomechanical test (ultimate load, elastic modulus, energy to failure, and stiffness) to detect bone regeneration in the distraction area., Results: The rats in all groups survived until the termination of the experiment. ELISA showed that the contents of HIF-1α, VEGF, CD31, and Osterix in the serum of the AT group were significantly higher than those of the DFO group and control group at the 4th and 6th weeks of the consolidation phase ( P <0.05). General observation, X-ray films, Micro-CT, and biomechanical test showed that bone formation in the femoral distraction area was significantly better in the DFO group and AT group than in the control group, and complete recanalization of the medullary cavity was achieved in the AT group, and BMD, BV/TV, Tb.Sp, Tb.N, and Tb.Th, as well as ultimate load, elastic modulus, energy to failure, and stiffness in the distraction area, were better in the AT group than in the DFO group and control group, and the differences were significant ( P <0.05). HE staining showed that trabecular bone formation and maturation in the distraction area were better in the AT group than in the DFO group and control group. Immunohistochemical staining showed that at the 4th week of consolidation phase, the expression levels of HIF-1α, VEGF, OCN, and OPN in the distraction area of the AT group were significantly higher than those of the DFO group and control group ( P <0.05); however, at 6th week of consolidation phase, the above indicators were lower in the AT group than in the DFO group and control group, but there was no significant difference between groups ( P >0.05)., Conclusion: Both continuous local perfusion of DFO in the distraction area and AT during the consolidation phase can activate the HIF-1α/VEGF signaling pathway. However, AT is more effective than local perfusion of DFO in promoting the process of angiogenesis, osteogenesis, and bone remodelling.

A series of β -cyclodextrin ( β -CD)-conjugates were prepared by combining three abietane-type diterpene acids with two azide-functionalized β -CDs via click chemistry, and the antiviral activity against wild-type and omicron SARS-CoV-2 spike pseudovirus as well as the antibacterial activity against Escherichia coli were investigated. All the synthesised conjugates exhibited no significant cytotoxicity to BHK-21-hACE2 cells with cell viability over 80% at concentration of 15  µ M. Among the conjugates, the heptavalent β -CD-dehydroabietic acid conjugate 6b exhibited higher anti-SARS-CoV-2 activity against the omicron variant compared to the other conjugates. This study suggested that the multivalent diterpene acid derivatives may have potential application against coronaviruses as entry inhibitors.

The development of cancer neoantigen vaccines that prime the anti-tumor immune responses has been hindered in part by challenges in delivery of neoantigens to the tumor. Here, using the model antigen ovalbumin (OVA) in a melanoma model, we demonstrate a chimeric antigenic peptide influenza virus (CAP-Flu) system for delivery of antigenic peptides bound to influenza A virus (IAV) to the lung. We conjugated attenuated IAVs with the innate immunostimulatory agent CpG and, after intranasal administration to the mouse lung, observed increased immune cell infiltration to the tumor. OVA was then covalently displayed on IAV-CPG using click chemistry. Vaccination with this construct yielded robust antigen uptake by dendritic cells, a specific immune cell response and a significant increase in tumor-infiltrating lymphocytes compared to peptides alone. Lastly, we engineered the IAV to express anti-PD1-L1 nanobodies that further enhanced regression of lung metastases and prolonged mouse survival after rechallenge. Engineered IAVs can be equipped with any tumor neoantigen of interest to generate lung cancer vaccines., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)